We propose to continue our investigations on the mechanism of estrogen biosynthesis in the human placenta. We will compare properties of the estrogen biosynthesizing system (aromatase) with the 1 beta- hydroxylase to determine if there is a relationship. We are extending our studies to the rat ovary and wish to compare the properties of the aromatase from this tissue with those already determined for the placental system. In connection with our work on the rat ovary, we will investigate methods of stimulating its activity with gonadotropins. Estrogens have important biochemical and clinical effects and the ultimate objective of our work is to develop methods for controlling their production. By so doing, we should be able to contribute to the control of their effects in such diverse research and clinical areas as reproduction, heart failure and cancer. Based on our knowledge of estrogen biosynthesis we have been able to control production in vitro by the use of synthetic steroidal inhibitors which we have developed. We propose to continue our synthesis and evaluation program to obtain ones which will have potent in vivo effects.